The onset of puberty at the normal age is very important, as any deviation from peer age can result in psychological perturbation. Moreover, disorders associated with precocious and delayed puberty, and many diseases such as polycystic ovarian syndrome, epilepsy, autism, and schizophrenia that originate at or worsen with puberty, are considerable clinical concerns. For these reasons, investigations of the mechanisms controlling the onset of puberty, using the non-human primate as a model, are essential and would contribute to the understanding and management of human clinical cases. The long-term objective of this research is to investigate the role of the hypothalamus in the control of the onset of puberty. The objective of this project is to study the hypothesis that kisspeptin-54 is responsible for triggering puberty in the rhesus monkey. Although previously, we have found that the reduction in GABAergic inhibition occurs at the time of the pubertal increase in LHRH release, the question of what triggers the onset of puberty is still unclear. Recent clinical studies indicate that GPR54 and its ligand kisspeptin-54 may be important for the mechanism of the onset of puberty in humans. The proposed study will investigate 1) whether sensitivity of LHRH neurons to kisspeptin-54 changes with developmental ages, 2) whether the pubertal increase in kisspeptin-54 is independent from the ovarian steroid hormone feedback system, 3) whether kisspeptin-54 increases in association with puberty, and 4) whether the pubertal increase in kisspeptin precedes the pubertal reduction in GABA release. In vivo release of LHRH and kisspeptin-54 from the stalk-median eminence will be assessed in female rhesus monkeys at different developmental ages. Results from the proposed project will provide insight into the mechanisms through which the hypothalamus controls gonadotropin release in primates and ultimately will lead to a new diagnostic tool as well as to a treatment strategy for disorders associated with puberty.